title: A framework for scalable parameter estimation of gene circuit models using structural information.
abstract: BACKGROUND
  Systematic and scalable parameter estimation is a key to construct complex gene regulatory models and to ultimately facilitate an integrative systems biology approach to quantitatively understand the molecular mechanisms underpinning gene regulation.
  
  
  RESULTS
  Here, we report a novel framework for efficient and scalable parameter estimation that focuses specifically on modeling of gene circuits. Exploiting the structure commonly found in gene circuit models, this framework decomposes a system of coupled rate equations into individual ones and efficiently integrates them separately to reconstruct the mean time evolution of the gene products. The accuracy of the parameter estimates is refined by iteratively increasing the accuracy of numerical integration using the model structure. As a case study, we applied our framework to four gene circuit models with complex dynamics based on three synthetic datasets and one time series microarray data set. We compared our framework to three state-of-the-art parameter estimation methods and found that our approach consistently generated higher quality parameter solutions efficiently. Although many general-purpose parameter estimation methods have been applied for modeling of gene circuits, our results suggest that the use of more tailored approaches to use domain-specific information may be a key to reverse engineering of complex biological systems.
  
  
  BACKGROUND
  http://sfb.kaust.edu.sa/Pages/Software.aspx.
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Computer, Electrical and Mathematical Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kuwahara
authors.forename: Ming
authors.initials: M
authors.lastname: Fan
authors.forename: Suojin
authors.initials: S
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Gao
mesh_terms: D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D008957:Models, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D049490:Systems Biology